(R)-Salbutamol, levosalbutamol or (R)-albuterol is α-[[(1,1-dimethylethyl)-amino]methyl-4-hydroxy-1,3-benzenedimethanol, belongs to the β-2-agonists used pharmaceutically as bronchodilators and is of considerable commercial interest. The chemical structure of the chiral α-aminoalcohol (R)-salbutamol is shown in formula I:

The methods of preparing (R)-salbutamol known in the art include the racemate cleaving of racemic salbutamol using di-toluyltartaric acid, e.g. according to U.S. Pat. No. 5,399,765. In addition, International Patent Application WO 95/29146 proposes the preparation of (R)-salbutamol starting from corresponding alpha-iminoketone by enantioselective reduction with boranes in the presence of a chiral oxaborazole catalyst.
However, the processes described in the art are not suitable for preparing (R)-salbutamol on an industrial scale as half the valuable starting product is lost during the racemate cleaving and large amounts of the oxaborazole catalyst, which is difficult to obtain, have to be used during the enantioselective reduction.
One of the primary objectives of the present invention is to develop a process by means of which (R)-salbutamol can be prepared with a high degree of optical and chemical purity. This is intended, for example, to minimise the danger of drugs which contain (R)-salbutamol as active substance being contaminated with the unwanted D-enantiomer.
Another aim of the invention is to develop a process by means of which (R)-salbutamol can easily be prepared in substantially enantiomerically pure form from starting materials which are easily obtained.
Another aim of the invention is to prepare (R)-salbutamol by means of a stereoselective process in order to avoid reaction steps in which chiral intermediate compounds or the chiral end product (R)-salbutamol is obtained as a racemate in a similar amount to the corresponding antipode.
Surprisingly it has now been found that (R)-salbutamol can be obtained on an industrial scale in very good yields and with good optical purity if salbutamone is subjected to asymmetric hydrogenation in the presence of rhodium and a chiral, bidentate phosphine ligand as catalyst system.